Methods and compositions for pain management

Abstract

The present invention provides novel methods and diagnostic kits for the objective measurement of the severity of pain or stress being experienced by a patient with a disorder, diagnosis and treatment for patients suffering from painful disorders, and monitoring the effectiveness of different pain-treatment protocols. Pain-measuring methods comprise collecting a sample from a patient and determining the presence of a pain-associated marker in the sample. Methods for alleviating pain comprise administrating a dose of a therapeutically effective amount of a composition to the patient wherein the dose is determined by the presence of a pain-associated marker in a biological sample obtained from the patient. Compositions for alleviating pain comprise substances that are pain-associated markers or agents that interfere with pain-associated markers, and block or modulate the progression of pain perceived by the patient.

We claim:  
     
       1. A method for identifying a marker that correlates with the intensity of a pain perceived by a patient comprising the steps of: 
       collecting a serum sample from the patient;  
       separating the components within said serum sample by electrophoresis in a gel;  
       reacting the gel with a diazonium salt and a substrate for a period of time to form a detectable band comprising an insoluble diazonium complex; and  
       identifying the size and location of the detectable band to identify said marker.  
     
     
       2. The method of  claim 1  wherein the gel has a gradient polymer density. 
     
     
       3. The method of  claim 1  wherein the diazonium salt is 4-chloro-2-methylaniline. 
     
     
       4. The method of  claim 1  wherein reacting is terminated by adding a reagent to the gel wherein said reagent is selected from the group consisting of acetic acid, formic acid and citric acid and mixtures thereof. 
     
     
       5. The method of  claim 1  further comprising performing densitometry analysis on said gel. 
     
     
       6. A method of diagnosing the extent of activation of the pain sensing neurological pathway in a patient comprising: 
       i) determining the amount of a cholinesterase pain marker in a biological sample obtained from said patient;  
       ii) comparing the amount of the cholinesterase pain marker in said sample to a threshold amount of cholinesterase pain marker; and  
       iii) assigning a pain status to the patient based upon the comparison, wherein the threshold amount of cholinesterase pain marker is determined by measuring the amount of cholinesterase in samples from patients in whom the pain sensing neurological pathway is not activated and setting the threshold so that the threshold amount of cholinesterase pain marker is at least three standard deviations above the mean cholinesterase amount in samples from normal individuals.  
     
     
       7. The method of  claim 6 , wherein additional amounts of cholinesterase pain marker are identified as indicative of increasing levels of pain sensing neurological pathway activation by comparing the mean amount of cholinesterase pain marker in individuals with higher levels of pain sensing neurological pathway activation with mean of cholinesterase pain marker in individuals with lower levels of pain sensing neurological pathway activation and selecting an amount between the two means. 
     
     
       8. The method of  claim 6 , wherein the pain sensing neurological pathway is activated by chronic spinal pain. 
     
     
       9. The method of  claim 8 , wherein the sample is blood or serum and the cholinesterase is serum cholinesterase. 
     
     
       10. The method of  claim 9 , wherein threshold amount of cholinesterase pain marker is 1272 and patients from whom the sample contains less than this amount of serum cholinesterase are deemed to have normal activation levels of the pain sensing neurological pathway while patients from whom the sample contains greater than this amount of serum cholinesterase are deemed to have high or activated activation levels of the pain sensing neurological pathway. 
     
     
       11. The method of  claim 6  further including the step of separating components within the biological sample. 
     
     
       12. The method of  claim 11  wherein separating comprises an electrophoretic separation. 
     
     
       13. The method of  claim 6 , wherein the cholinesterase in the biological sample is reacted with a substrate to produce a detectable product. 
     
     
       14. The method of  claim 6 , wherein the threshold amount of cholinesterase pain marker is based upon a normal individual sample obtained from the same patient prior to activation of the pain sensing neurological pathway. 
     
     
       15. The method of  claim 6 , wherein the activation of the pain sensing neurological pathway is caused by the presence of a lesion. 
     
     
       16. The method of  claim 6 , whereby cholinesterase is distinguished and measured by escrine sensitivity. 
     
     
       17. A diagnostic kit for determining the level of activation of the pain sensing neurological pathway in a patient comprising at least one antibody that binds to cholinesterase in a biological sample obtained from the patient wherein the amount of cholinesterase in the sample is then compared with an amount of cholinesterase known to be indicative of activation of the pain sensing neurological pathway. 
     
     
       18. The diagnostic kit of  claim 17 , wherein the antibody or antibodies are polyclonal antibodies, monoclonal antibodies or fragments of polyclonal or monoclonal antibodies. 
     
     
       19. The method of  claim 17  wherein cholinesterase is distinguished and measured based upon eserine sensitivity. 
     
     
       20. A method of diagnosing the extent of activation of the pain sensing neurological pathway in a patient comprising: 
       i) determining the amount of a pain marker in a biological sample obtained from said patient;  
       ii) comparing the amount of the pain marker in said sample to at least one pre-determined pain marker amount;  
       iii) assigning a pain status to the patient based upon the comparison.  
     
     
       21. A method for determining the efficacy of a treatment for pain comprising: 
       i) determining the amount of a pain marker in a first biological sample obtained from said patient;  
       ii) administering the treatment to said patient;  
       iii) determining the amount of a pain marker in a second biological sample obtained from said treated patient; and  
       iv) comparing the amount of the pain marker in the first and second biological samples.  
     
     
       22. A diagnostic kit for determining the level of activation of the pain sensing neurological pathway in a patient comprising at least one agent that reacts with cholinesterase in a biological sample obtained from a patient wherein the amount of cholinesterase in the sample is then compared with an amount of cholinesterase known to be indicative of activation of the pain sensing neurological pathway. 
     
     
       23. A method of diagnosing the extent of activation of the pain sensing neurological pathway in a patient comprising: 
       i) determining the amounts of at least two pain markers in a biological sample obtained from said patient;  
       ii) comparing the amounts of the at least two pain marker in said sample to a pre-determined amount of each pain marker  
       iii) assigning a pain status to the patient based upon the comparison.